ABSTRACT

At the neurosecretory terminals in the neural lobe,
oxytocin secretion is restrained by co-secreted endogenous opioids, which
act via kappa-receptors. The co-secreted opioids include products of pro-dynorphin
(released by both vasopressin and oxytocin terminals) and proenkephalin
(released by oxytocin terminals). In morphine-tolerant rats this opioid
mechanism is more effective, but in late pregnancy it is less effective.
Opioids also act directly on oxytocin cell bodies, via separate mu- and
kappa-receptors, inhibiting excitation by all stimuli tested, and also exert
presynaptic and more distal actions on afferent systems. During chronic
morphine exposure, tolerance and dependence develop in oxytocin neurones;
the former involves reduction in mu-opioid receptor density, while the latter
may involve compensatory upregulation of mechanisms regulating Ca2+ influx.
In mid-pregnancy, the effectiveness of opioid mechanisms in the neural lobe
increases, assisting the accumulation of oxytocin stores in advance of parturition,
but by the end of pregnancy the effectiveness of these mechanisms is reduced.
At this time, a separate endogenous opioid system, acting via mu-receptors,
actively restrains the electrical activity of oxytocin neurones. Release
of this endogenous opioid inhibition may contribute to the increase in activity
during parturition analogous to that occurring during morphine withdrawal
excitation. Central opioid mechanisms retain the ability to control oxytocin
neurones during parturition, and can interrupt established parturition by
inhibiting oxytocin neurone firing rate in disadvantageous environmental
circumstances.